Topically active carbonic anhydrase inhibitors. 3. Benzofuran- and indole-2-sulfonamides.
Derivatives of benzofuran- and indole-2-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. These compounds were found to be excellent inhibitors of carbonic anhydrase and to lower intraocular pressure in a rabbit model of ocular hypertension. However, the development of these compounds for clinical use was precluded by the observation that they cause dermal sensitization in guinea pigs. A correlation between electrophilicity, as assessed by in vitro reactivity with reduced glutathione, and dermal sensitization potential was further documented.
Graham
S L
SL
Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
Hoffman
J M
JM
Gautheron
P
P
Michelson
S R
SR
Scholz
T H
TH
Schwam
H
H
Shepard
K L
KL
Smith
A M
AM
Smith
R L
RL
Sondey
J M
JM
D000287:Administration, Topical; D000818:Animals; D001572:Benzofurans / Q000009:adverse effects; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D002627:Chemistry, Physical; D004342:Drug Hypersensitivity; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000009:adverse effects; D007700:Kinetics; D009798:Ocular Hypertension / Q000188:drug therapy; D010084:Oxidation-Reduction; D011817:Rabbits; D013329:Structure-Activity Relationship; D013449:Sulfonamides
D001572:Benzofurans; D002257:Carbonic Anhydrase Inhibitors; D007211:Indoles; D013449:Sulfonamides; D005978:Glutathione